Asthma Drug Zileuton Stops Food Allergy Reactions In Mice. Could It Work In Humans?

A mouse study finds a gut “gatekeeper” that decides whether allergens can get through — and an existing drug that could block dangerous reactions before they start.

* In mice, a “gut gatekeeper” controls whether allergens can cross into the body and trigger a reaction.

* The protective version of this gatekeeper is linked to a more active enzyme (DPEP1) that clears chemical signals which open the gut barrier.

* Blocking those signals with an existing asthma drug (zileuton) stopped allergic reactions from oral exposure in mice.

* While promising, the findings are in mice; human safety and effectiveness are unknown.

CHICAGO — For millions of Americans with food allergies, eating can feel like walking through a minefield. Even people with the same allergy can have very different experiences; some react to the tiniest crumb, while others can handle small amounts without any symptoms. Now, scientists at Northwestern University and Yale have uncovered a clue in mice that could help explain this mystery.

Researchers discovered a biological pathway in the gut that acts like a bouncer, deciding which food proteins get past the intestinal wall to trigger an allergic reaction. And they found that an asthma drug already approved by the FDA, called zileuton, could block this process in mice, though it’s far too soon to say whether it would work in people.

The research focused on a group of inflammation-triggering molecules called cysteinyl leukotrienes. In mice, these molecules can open the gates for allergens, making it easier for them to cross the gut lining and set off the immune system. Block the molecules, and the gut stays on lockdown.

The clue came from two common types of lab mice. One type, dubbed C57BL/6, almost never reacted to peanut protein when it was eaten, even though their immune system clearly recognized it. The other type, C3H/HeJ, often had severe, body-wide reactions when given the same food.

Both strains made similar levels of antibodies and had healthy immune systems. The difference was in their guts. In one test using ovalbumin, a protein found in egg whites, the mice in the first group absorbed more than 100 times less ovalbumin than the other group, a striking difference in how much allergen slipped through.

When the team dug into the genetics, they found a key player: a gene called Dpep1. This gene makes an enzyme that normally breaks down the very molecules that help allergens cross the gut wall.

The “protected” mice had a version of this enzyme that cleared the signals quickly, keeping their gut barrier tight. The “vulnerable” mice had a version that left more of those signals hanging around, making it easier for allergens to sneak through.

To see what would happen if they interfered with this process, the scientists tried two drugs. One, cilastatin, blocks the protective enzyme. When resistant mice got it, more allergen got through their gut wall. The other, zileuton, stops the chemical signals from being made in the first place. When the vulnerable mice got zileuton before eating the allergen, they stayed symptom-free during oral testing.

New Food Allergy Treatment for People On the Horizon? All of the main experiments were in mice, but there are hints the same mechanism could matter in humans. People and the “vulnerable” mice share the same version of the Dpep1 gene, and tissue samples from the human gut showed a similar pattern to those mice.

In a small group of children with peanut allergies, those who reacted to even tiny amounts of peanut showed increased activity in certain genes linked to producing the “open sesame” signals after eating peanut. This doesn’t prove cause and effect, but it lines up with what the mouse experiments found.

Right now, living with a food allergy mostly means avoiding the trigger food and keeping emergency medication like an EpiPen on hand. Some patients try oral immunotherapy to build tolerance, but it doesn’t work for everyone and can sometimes trigger dangerous reactions.

This study points to a different tactic: keep allergens from getting past the gut wall in the first place. In the mouse tests, a carefully timed dose of zileuton (given an hour before eating the allergen) completely blocked signs of a reaction from eating it. The drug didn’t help if the allergen was injected directly into the body, showing it works by protecting the gut rather than suppressing the immune system as a whole.

Zileuton is already approved for asthma, so we know it can be used safely in that context, but human trials would be needed before it could ever be used for food allergies.

It’s worth noting that some factors like exercise, alcohol, or certain medicines are known to make allergic reactions worse by making the gut wall leakier. Some of these also influence the same chemical signals found in this study, so it’s possible they connect — but that’s still just a theory.

For the roughly 32 million Americans with food allergies, this discovery offers a new way to think about prevention: not just calming down an overactive immune system, but also strengthening the gut’s front-line defenses.

Disclaimer: This article is based on a laboratory study conducted in mice. While the findings suggest a possible new way to prevent food allergy reactions, the results may not apply to humans. The drug mentioned (zileuton) is FDA-approved for asthma, but has not been tested for preventing food allergies in people. More research, including human clinical trials, is needed before any conclusions can be made about its safety or effectiveness for this purpose.

Ask your doctor if this medication is right for you.

Rare Side Effects include:

Temporary paralysis in limbs
Chronic hiccups
Involuntary eye twitching
Abnormal hair growth (e.g., excessive facial hair)
Loss of fingernails or toenails
Extreme sensitivity to cold or heat
Sleepwalking
Uncontrollable giggling
Temporary loss of taste for spicy foods
Skin discoloration (e.g., turning slightly blue or green)
Sudden urge to reorganize furniture
Excessive yawning
Feeling of "pins and needles" across the entire body
Temporary inability to whistle
Increased sensitivity to bad puns

Extremely Rare and Hypothetical Side Effects may include:

Ingrown toenails (even in people who trim nails regularly)
Spontaneous ability to speak in rhyming couplets
Temporary transformation of hair into cotton candy texture
Uncontrollable urge to tap-dance in public
Eyes glowing faintly in the dark
Sudden craving for obscure fruits (e.g., durian or kumquat)
Toes curling permanently into a spiral shape
Skin developing a glittery sheen under moonlight
Ability to hear distant dog whistles
Fingernails growing at triple speed
Temporary levitation (up to 2 inches off the ground)
Unexplained attraction to polka music
Teeth vibrating when near a microwave
Spontaneous growth of a third eyebrow
Sneezing glitter or confetti
Temporary ability to predict the weather by smelling rain
Feet emitting a faint popcorn-like odor
Uncontrollable urge to collect rare coins
Hair changing color based on mood
Sudden fluency in a fictional language (e.g., Klingon)
Ears twitching in sync with nearby clocks
Skin temporarily turning plaid
Unexplained craving for jellybeans at 3 a.m.
Toes developing a magnetic attraction to metal objects
Spontaneous teleportation to the nearest coffee shop (within 5 miles)
Eyebrows growing into perfect geometric shapes
Voice developing an echo in large rooms
Temporary ability to communicate with houseplants
Fingernails emitting a faint glow under UV light
Sudden obsession with knitting tiny sweaters for pets

Other Considerations:

Psychological effects: May include vivid dreams, temporary obsession with obscure trivia, or an urge to write poetry about clouds.
Dermatological effects: Rare cases of skin developing a velvet-like texture or emitting a faint lavender scent.
Gastrointestinal effects: May cause burps that smell like cinnamon or farts that sound like a kazoo.
Neurological effects: Rare reports of patients solving complex math problems in their sleep or forgetting how to tie shoelaces for 24 hours.
Musculoskeletal effects: May cause joints to creak like old floorboards or muscles to hum softly during exercise.
Cardiovascular effects: Heart may briefly beat in sync with nearby music or pulse in Morse code.
Endocrine effects: Possible temporary growth of a single, unicorn-like hair on the forehead.
Immune effects: Rare chance of becoming temporarily immune to mosquito bites but allergic to polyester.

Warnings:

Stop taking this medication immediately if you experience sudden teleportation, glowing bones, or the ability to talk to squirrels.
Consult your doctor if you develop an urge to alphabetize your sock drawer or if your shadow starts moving independently.
Avoid operating heavy machinery if you experience spontaneous tap-dancing or an urge to yodel.
This medication may cause you to believe you’re a minor character in a sci-fi novel; this is usually temporary.
Do not combine with other medications, such as Unicornium or Dragonix, as this may amplify absurd effects.

Note: This is a purely fictional list created for entertainment purposes, blending realistic side effects with absurd, humorous ones and has nothing to do with the medication presented in this article.

You've been warned!!

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